There is a market need, such as, one dictated by the Federal Drug Administration (FDA), to maintain the accuracy of sensors that are defined as current Good Manufacturing Practices (cGMP) values in a validated pharmaceutical process. Today, this is achieved by various methods, such as, (1) installing ‘certified’ instruments, and (2) maintaining a costly routine calibration protocol.
Additionally, the Food and Drug Administration's Process Analytical Technology (PAT) initiative has opened the door to a fresh look at applying technology for productivity improvements, especially, in the pharmaceutical industry. The application of on-line, real time analytical instruments was the first PAT initiative. This invention addresses another problem—data integrity. This invention takes a novel approach to maintaining data integrity through the use of redundancy and statistical analysis. The result is reduced calibration cost, increased data integrity and reduced off-spec uncertainty.
Today, pharmaceutical companies write elaborate calibration protocols that are consistent (and sometimes overly compliant) with FDA cGMP guidelines to maintain the reported process value integrity. This can result is extremely high cost for compliance with only a minimum ROI for improved productivity or product quality. For example, one pharmaceutical site in New Jersey conducts about 2900 calibrations per month. Of those, about 500 are demand maintenance where the instrument has clearly failed as evidence by a lack of signal or a digital diagnostic (catastrophic failures). The remaining 2400 calibrations are scheduled per protocol. Of these, only about 400 calibrations find the instrument out of calibration. The majority, about 2000, calibrations per month find the instrument still working properly.
With this invention an alternate instrument scheme is provided which basically consists of the use of redundant sensors and statistical analysis to avoid unnecessary calibrations and to detect sensors that are starting to drift before they go out of calibration.
Additionally, there is also a need for a manufacturing process which utilizes calibration and monitoring instruments to reduce the cost and complexity.
This invention overcomes the problems of the prior art and provides an inventive use of statistics to determine calibration of instruments.